One premise underlying this proposal is that formation of fibrin is an irreversible process; as a result, the structure of fibrin is determined by a self-assembly process. In order to understand the assembly, we must determine the nature of the intermediates, the rates at which intermediates and product are formed, and the equilibria between species. This will be done by observing the assembly at low concentrations (where it is slow). We also wish to improve our understanding of the structure of fibrin, and how it depends on the assembly process. Important structural details are: the conformation of monomeric fibrin, the overall shape of the molecule in solution and in the fiber, the packing of molecules in the fiber (spacings and symmetry), fiber diameter, fiber length between branchpoints and the structure at the branchpoints. We shall use light scattering in order to follow the formation of fibers and to measure fiber thickness, electron microscopy to determine size and shape of fibers to different stages of the assembly and to study nature and frequency of network branchpoints, elasticity measurements to detect and follow the formation of the fiber network. We shall investigate methods for preparing fibrin in a form suitable for X-ray diffraction studies. We shall devote a major part of our effort to study physiologically important interactions of fibrin with other plasma components using these physical techniques, following at the same time changes in the chemistry of fibrin with biochemical techniques. Blood components whose interactions with fibrin we shall study include: fibrin degradation products, calcium ion and platelet proteins. We shall also study the effects of random-coil water-soluble polymers (polyethyleneglycol, dextran) on fibrin formation and structure.